KMT2B Rare Missense Variants in Generalized Dystonia

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00064165%3A_____%2F17%3A10361107" target="_blank" >RIV/00064165:_____/17:10361107 - isvavai.cz</a>

Nalezeny alternativní kódy

RIV/00216208:11110/17:10361107 RIV/00023884:_____/12:00007435

Výsledek na webu

<a href="http://dx.doi.org/10.1002/mds.27026" target="_blank" >http://dx.doi.org/10.1002/mds.27026</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1002/mds.27026" target="_blank" >10.1002/mds.27026</a>

Jazyk výsledku

angličtina

Název v původním jazyce

KMT2B Rare Missense Variants in Generalized Dystonia

Popis výsledku v původním jazyce

Background: Recently a novel syndrome of childhood-onset generalized dystonia originating from mutations in lysine-specific methyltransferase 2B (KMT2B) has been reported. Methods: We sequenced the exomes of 4 generalized dystonia-affected probands recruited from a Prague movement disorders center (Czech Republic). Bioinformatics analyses were conducted to select candidate causal variants in described dystonia-mutated genes. After cosegregation testing, checklists from the American College of Medical Genetics and Genomics were adopted to judge variant pathogenicity. Results: Three novel, predicted protein-damaging missense variants in KMT2B were identified (p.Glu1234Lys, p.Ala1541Val, p.Arg1779Gln). Meeting pathogenicity criteria, p.Glu1234Lys was absent from population-based controls, situated in a key protein domain, and had occurred de novo. The associated phenotype comprised adolescence-onset generalized isolated dystonia with prominent speech impairment. Although linked to a similar clinical expression, p.Ala1541Val and p.Arg1779Gln remained of uncertain significance. Conclusions: Rare missense variation in KMT2B represents an additional cause of generalized dystonia. Application of sequence interpretation standards is required before assigning pathogenicity to a KMT2B missense variant.

Název v anglickém jazyce

KMT2B Rare Missense Variants in Generalized Dystonia

Popis výsledku anglicky

Background: Recently a novel syndrome of childhood-onset generalized dystonia originating from mutations in lysine-specific methyltransferase 2B (KMT2B) has been reported. Methods: We sequenced the exomes of 4 generalized dystonia-affected probands recruited from a Prague movement disorders center (Czech Republic). Bioinformatics analyses were conducted to select candidate causal variants in described dystonia-mutated genes. After cosegregation testing, checklists from the American College of Medical Genetics and Genomics were adopted to judge variant pathogenicity. Results: Three novel, predicted protein-damaging missense variants in KMT2B were identified (p.Glu1234Lys, p.Ala1541Val, p.Arg1779Gln). Meeting pathogenicity criteria, p.Glu1234Lys was absent from population-based controls, situated in a key protein domain, and had occurred de novo. The associated phenotype comprised adolescence-onset generalized isolated dystonia with prominent speech impairment. Although linked to a similar clinical expression, p.Ala1541Val and p.Arg1779Gln remained of uncertain significance. Conclusions: Rare missense variation in KMT2B represents an additional cause of generalized dystonia. Application of sequence interpretation standards is required before assigning pathogenicity to a KMT2B missense variant.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

30103 - Neurosciences (including psychophysiology)

Projekt

<a href="/cs/project/GA16-13323S" target="_blank" >GA16-13323S: Mikro a makro konektomika subtalamického jádra u člověka: vliv neuromodulace a dopaminové deplece</a><br>

Návaznosti

P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)

Rok uplatnění

2017

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Název periodika

Movement Disorders

ISSN

0885-3185

e-ISSN

—

Svazek periodika

32

Číslo periodika v rámci svazku

7

Stát vydavatele periodika

US - Spojené státy americké

Počet stran výsledku

5

Strana od-do

1087-1091

Kód UT WoS článku

000405488300018

EID výsledku v databázi Scopus

2-s2.0-85019931873